One goal of our Center is to determine the role of inhibitory neuronal systems and receptors in genetic differences in alcohol sensitivity. This research direction has arisen from our collective work showing differences between LS and SS mice in GABAa receptors. In this project, we propose to link and extend ongoing studies in the ARC by asking if any of five major QTLs for ethanol sensitivity determine functional differences in GABAa receptors. This approach will utilize congenic mice from component 3 for biochemical studies of GABAa receptor function. In addition, we will focus on the roles of the two variants of the gamma subunit of the GABAa receptor in alcohol sensitivity in vivo and in vitro. These studies will be based on transgenic mice that overexpress either the gamma2S or gamma2L subunit. Effects of these transgenes will be evaluated on several different genetic backgrounds including 129SvevTac, C57BL/6J, ILS, and ISS. These mice will also be provided to other projects in the ARC.